Dementia Japan 23: 38-46, 2009

The 10th anniversary of Aβ immunotherapy :does Aβ immunization activate brain phagocytes ?

Haruhiko Akiyama

Tokyo Institute of Psychiatry

    Aβ immunotherapy is, at present, one of the most hopeful strategies to fight against Alzheimer's disease (AD). The mechanism by which Aβ immunotherapy removes the Aβ deposits from the brain has yet to be determined, however. Two hypotheses have been tested repeatedly: Fc-γ receptor-mediated Aβ removal by microglia and the enhanced Aβ efflux from the brain to the periphery. In the AD brain without immunization, the Aβ deposits are opsonized by complement proteins, one of the phagocytic mechanisms, which is not very efficient. The antibody-mediated phagocytosis is far more efficient, and, thus, it seems reasonable to speculate that a small amount of anti-Aβ antibodies enter the brain and enhance microglial removal of the Aβ deposits. A lot of evidences for and against the enhanced phagocytosis by Aβ immunotherapy have been accumulated. Further study is needed to elucidate the effect of immunotherapy to the Aβ dynamics in the brain.

Address correspondence to Dr. Haruhiko Akiyama, Tokyo Institute of Psychiatry (2-1-8 Kamikitazawa, Setagaya-ku, Tokyo 156-8585, Japan)